tbuckley/cabot-search huggingface dataset:
SURG-06. Management outcome (5years or more) of paediatric vertebral haemangiomas presenting with myelopathy
Authors: Pankaj Singh, Sarat Chandra, Shashank Kale
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Vertebral hemangiomas are very rare in pediatric age group. In this study we analysed the outcomes of patient treated at department of neurosurgery , All india institute of medical sciences New Delhi since may 2010 to January 2022 with at least 5 year follow up. MATERIALS AND METHOD: All patients up to 18 years age of vertebral haemangioma treated at our hospital from may 2010 to january 2022 with at least 5 year follow up. All had features of myelopathy.Patients demography, clinical details and follow up and complications were retrieved from hospital records. Functional clinical outcomes were measured using ASIA score. Mean age was 14.21 years with range of 12 years to 18 years. All patients had magnetic resonance imaging and computed tomography of spine in preoperative and postoperative period. Mean follow up was 78 months with range from 60 month to 144 months. RESULTS: There were 6 male and 8 female patients with sex ratio of 3:4. All were located in dorsal spine with single level involvement . Upper dorsal spine involvement was more common (10 cases 71.43%) than lower dorsal spine involvement (4 case 28.57%). All patients had weakness of lower limbs with features of myelopathy, urinary bladder symptoms were present in 6 patients local site pain in 1. D1 involvement was present in 1, D3 in 2, D4 in 2, D5 in 2, D6 in 3 , D8 in 1,D10 in 1,D11 in 1 and D12 in 1. All patients have improvement in power of both lower limbs after surgery. Bladder symptom and pain resolved in all patients. CONCLUSION: Good postoperative results can be achieved in pediatric symptomatic vertebral hemangioma with minimal complications. Individualization of treatment for each patient should be done with avoidance of selecting more blood loss procedures like corpectomies.
Impact of cancer susceptibility gene (CSG) mutations in advanced NSCLC (aNSCLC).
Authors: Danielle Klingberg, Janene Dalrymple, Milita Zaheed, Craig R. Lewis, Tom John, Chee Khoon Lee
Journal: Journal of Clinical Oncology (2022)

9131 Background: Next generation sequencing (NGS) is used widely to identify somatic oncogenic driver mutations in aNSCLC to guide treatment. Comprehensive profiling has led to identification of multiple gene mutations of unclear significance, including germline genes associated with cancer risk, termed CSG. Using data from two randomized trials comparing atezolizumab to docetaxel, we investigated the prognostic and predictive values of CSG in aNSCLC. Methods: We used publicly available data from the OAK (NCT02008227) and POPLAR (NCT01903993) trials. At baseline, plasma was analyzed for cfDNA using FoundationOne CDx NGS assay. We defined CSGs as pathogenic variants of APC, BAP1, BRCA1/2, BRIP1, CDH1, CDKN2A, CHEK2, FH, FLCN, MEN1, MET, MSH2/6, MLH1, PMS2, PALB2, PTCH1, PTEN, RAD51, RB1, SDHB, SMARCA4, STK11, TSC1/2 and VHL. Cox models with treatment covariate, CSG status (mutant [mt] vs wild-type [wt]) and their interaction was used to assess the predictive value by treatment of CSG mt for overall survival (OS) and progression free survival (PFS) using univariate and multivariate models. Similar analysis was performed for objective response rate (ORR). Results: Of 1137 patients, 853 with sufficient tumor content formed the analysis population. In total, 295 (35%) had a known/likely pathogenic CSG mt. The variant allele frequencies (vAF) of CSG mt ≥30%, 10-30%, and &lt;10% were 8% (N=23), 25% (N=73), and 67% (N=199) respectively. Patients with CSG mt were more likely to be smokers (89% vs 81%, P=0.005), had squamous tumors (37% vs 26%, P=0.001) with higher blood-based tumor mutation burden (mean 13.8 vs 10.2 per megabase, P&lt;0.001). CSG mt was not predictive of greater OS benefit with atezolizumab over docetaxel (Table). CSG mt was associated with 35% increase risk of death in univariable analysis (HR 1.35, 95% CI 1.15-1.59). CSG mt was associated with inferior OS in multivariable analysis adjusting for performance status, smoking status, tumor histology, age, sex and number of organ sites of metastasis (HR 1.26, 95% CI 1.07-1.48). Conclusions: Plasma CSG mt is an independent poor prognostic factor in two large aNSCLC clinical trial datasets. Majority of vAF of CSG were low, suggesting that very few were potentially germline in origin, but dedicated sequencing for confirmation will be required. If confirmed, CSG status could be used as a stratification factor in future aNSCLC trials. [Table: see text]
EPEN-13. Clinically relevant molecular hallmarks of PFA ependymomas display intratumoral heterogeneity and correlate with tumor morphology
Authors: Swenja Gödicke, Max Ehlert, Denise Obrecht, Stefan Rutkowski, Ulrich Schüller
Journal: Neuro-Oncology (2022)

Abstract PFA ependymomas are aggressive posterior fossa tumors that mainly effect children and have a poor prognosis despite intensive therapy. Histopathology reveals glial neoplasms that usually show perivascular pseudorosettes throughout the tumor. Tumor cell density may vary within a tumor and sometimes shows well demarcated nodules of extremely densely packed tumor cells within surrounding loose glial tissue harboring diffusely distributed tumor cells. To determine potential molecular differences in such areas and to understand the clinical meaning, we analysed 70 clinically well-annotated PFA samples and 9 corresponding relapse samples. Areas of low and high cell density were digitally identified with a cut-off of 8,500 cells/mm². Global DNA methylation and copy-number profiling was performed in 52/79 cases for the entire tumor area of the sample and in 15/79 cases for the cell-dense and less cell-dense regions, separately. Fluorescence-in-situ-hybridization was performed for 20 cases, and scRNA-Seq data were analysed for 12 cases. The proportion of cell-dense areas proved to be highly variable on a continuum ranging from 0 % to 100 % of the tumor area. It was significantly higher in relapses in comparison to the respective primary tumors (p=0.036). Also, cell-dense areas displayed a significantly higher proportion of proliferating tumor cells (p&amp;lt;0.01). Global DNA methylation was similar, but not identical in different tumor areas. In 6/15 cases, the PFA subtype changed as determined by the current version of the brain tumor classfier (v12, www.molecularneuropathology.org). Chromosomal changes at 1q and 6q were only detectable in cell-dense areas in 5/12 and in 3/12 cases, respectively. Finally, scRNA-Seq data confirmed a widespread heterogeneity regarding 1q and 6q changes in PFA ependymoma cells. These data suggest that PFA ependymoma habor a previously unrecognized heterogeneity that has to be accounted for when selecting material for the analysis of clinically relevant DNA methylation profiles or copy number changes.
Effects of five prescriptions in <i>Synopsis of Golden Chamber</i> on the malignant phenotype and expression of CA125, CEA, HE4 proteins in human ovarian cancer cells.
Authors: Fuchun Si, Gao Si
Journal: Journal of Clinical Oncology (2022)

e17546 Background: Ovarian cancer(OC) is a common gynecological tumor with characteristics of low early diagnosis rate, late lack of effective treatment and high mortality. It is an important problem to find new effective treatment for ovarian cancer. Synopsis of the Golden Chamber is the miscellaneous diseases part of Treatise on Typhoid and Miscellaneous Diseases written by Zhang Zhongjing, a famous medical expert in Eastern Han Dynasty of China, and is also the earliest classical treatise on diagnosis and treatment of miscellaneous diseases, which records 205 prescriptions. This study aims to screen out formula with strong inhibitory effects on OC from 205 prescriptions of Synopsis of the Golden Chamber , and investigate the effects of screened prescriptions in Synopsis of the Golden Chamber on human ovarian cancer cell malignant phenotype and CA125, CEA and HE4 proteins expression. Methods: MTT method was applied to screen out the best effective prescription and determine the IC50 value of prescription on ovarian cancer ES-2 and OV-1063 cells. The effects of screened prescriptions on the proliferation, migration, invasion, cloning ability, cell cycle and CA125, CEA and HE4 proteins expression of ES-2 and OV-1063 cells were investigated by MTT assay, RTCA assay, soft agar assay, flow cytometry and western blot analysis. Results: Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction were screened out, which all could obviously inhibit the proliferation of ES-2 and OV-1063 cells with dose-effect and time-dependent manner. The IC50 values of Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction for ES-2 cell were 636.476, 315.859, 24.357, 9.519, 96.533μg/ml respectively; for OV-1063 were 403.119, 225.176, 12.977, 9.256, 115.86μg/ml respectively. The five prescriptions all significantly affected the cell morphology, proliferation, migration, invasion, cloning ability, cell cycle of ES-2 and OV-1063 cells. The five prescriptions all could decreased the protein expression levels of CA125 and CEA in ovarian cancer OV-1063 cells, while Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction and Baitouweng Decoction decreased the expression of HE4 protein in OV-1063 cells. Conclusions: The five prescriptions in Synopsis of the Golden Chamber can inhibit the malignant phenotype of ovarian cancer, which may be related to the inhibition of CA125, CEA and HE4 proteins expression.
A phase 1 first-in-human dose finding/randomized phase 2 study of IMM60 and pembrolizumab (PEM) in advanced melanoma and non–small cell lung cancer (NSCLC; IMP-MEL).
Authors: Nicholas Coupe, Ian B. Walters, Robert A. Kramer, Uzi Gileadi, Mark R. Middleton
Journal: Journal of Clinical Oncology (2022)

2582 Background: Invariant natural killer T-cells (iNKTs) share features of innate cells (NK-like) and T-cells (can prime and boost an adaptive immune response). The importance of this relatively rare lymphocyte subset has generated increased interest due to its dual ability to have a direct cytotoxic effect on CD1d expressing tumors and also its ability to induce long-lasting antitumor CD8 T cell responses mediated by cross priming and licensing of dendritic cells. Various clinical approaches involving the use of allogenic iNKT cells (both untransduced and CARs) are in development and here we describe initial clinical studies with IMM60, a synthetically derived agonist of iNKT cells which is formulated in a liposome( PORT-2). In preclinical studies, IMM-60 treatment results in maturation of DCs and B cells and a potent stimulation of iNKT cell-derived IFN-g. In efficacy studies, IMM60 demonstrated monotherapy activity in PD-1 resistant models, (eg., B16-F10), up-regulation of PD-L1 expression on cancer cells as a consequence of its priming effect, and was able to overcome resistance to PD-1 antibody therapy. Methods: IMP-MEL is an open-label first-in-man phase 1/2 study, currently enrolling adult subjects with advanced NSCLC and melanoma. IMM60 containing liposomes were administered IV Q3W at 3 escalating dose levels for 6 doses alone or with PEM 200mg Q3W. The study seeks to assess the safety and efficacy of IMM-60 alone and in combination with PEM. Results: 5 subjects have been enrolled in the monotherapy cohort having a median of 3 prior therapies (min 2, max 5). Median age was 64.5 years. No treatment related adverse events have been reported nor any objective disease responses in the evaluable monotherapy subjects (n=3) to date. Conclusions: IMM-60 is well tolerated when administered IV as monotherapy at the doses tested. The liposomal formulation leads to a favorable preliminary safety profile. Full results of the phase 1 will be reported at the meeting with analysis of circulating cytokines and flow cytometric analysis. The trial plans to transition to phase 2 testing IMM60-alone vs PEM monotherapy vs the combination of IMM60 with PEM. Clinical trial information: 80472712.
Overall survival results from a phase II trial of anlotinib plus sintilimab in patients with recurrent advanced cervical cancer.
Authors: Qin Xu, Chuan-ben Chen, Yang Sun, Zhangzhou Huang, Yibin Lin, Jing Liu, Li Li, Zirong Li, Junping Pan, Ying Chen
Journal: Journal of Clinical Oncology (2022)

5536 Background: The anlotinib (a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling) plus sintilimab (an antibody against PD-1) in patients with advanced cervical cancer trial was a multicenter, single-arm, phase II study (ChiCTR1900023015) that showed promising activity. The results of this trial have been previously reported and here we present updated survival data after a median follow-up of 13.0 months. Methods: Pts who have received at least once platinum-based chemotherapy, recurrent advanced cervical cancer, PD-L1 for CPS≥1, ECOG 0-1 were considered eligible for enrollment. Anlotinib was taken orally (10mg, qd, d1-14, 21 days per cycle), and sintilimab was administered intravenously (200mg, q3w, d1). The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), safety and biomarkers. Results: Between December 2019 and December 2020, 42 patients with a median age of 53 years (range 36 to 67 years) were enrolled and received study treatment (ITT population and safety population). The data cutoff date was February 10, 2022. The patients were followed up for median duration of 13.0 months (range 0.03 to 24.8 months). In the ITT population, 2 (4.8%) patients achieved CR and 21 (50%) attained PR, the confirmed ORR was 54.8% (95% CI 38.7% to 70.2%). Fourteen (33.3%) patients had SD and the DCR was 88.1% (95% CI 74.4% to 96.0%). In the efficacy-evaluable patients (n = 39), the ORR was 59% (95% CI 42.1% to 74.4%) and the DCR was 94.9% (95% CI 82.7% to 99.4%). The median PFS was 9.46 months (95% CI 8.2 to 11.9) and the 6-month PFS rate was 73.4% (95% CI 60.6% to 89.0%). OS events occurred in 18 patients (42.9%). The median OS was 17.4 months (95% CI 12.4 to not reached). The 12-month OS rate and 24-month OS were 71.8% (95% CI 59.0% to 87.4%) and 49.1% (95% CI 34.5% to 69.9%), respectively. Conclusions: Anlotinib plus sintilimab showed a long-term survival benefit for patients with recurrent advanced cervical cancer. Additional investigations in larger randomized controlled trials are warranted in the future. Clinical trial information: ChiCTR1900023015.
Squamous metaplasia in endometrial cancer changing local hormonal tumor profile.
Authors: Svetlana V. Kornienko, Elena M. Frantsiyants, Valeria A. Bandovkina, Tatiana I. Moiseenko, Meri L. Adamyan, Natalia V. Chernikova, Yuriy A. Poryvaev, Sergey V. Tumanyan, Natalia A. Maksimova, Konstantin P. Boyko, Viktor V. Gurnak, M. A. Arzamastseva, Anna S. Egorova, Ekaterina V. Verenikina, Anna Yu Ardzha, Oleg I. Kit
Journal: Journal of Clinical Oncology (2022)

e17621 Background: An imbalance of sex hormones in endometrial cancer (EC) towards hyperestrogenism together with progesterone deficiency is considered to stimulate proliferation and suppress endometrial apoptosis. EC with squamous metaplasia is characterized by a more severe clinical course and the lack of an adequate response to standard treatment. The purpose of this study was to analyze the local hormonal profiles of tumors with squamous metaplasia in patients with obesity. Methods: The main group included 20 EC patients with squamous metaplasia, and control group included 35 patients with endometrioid adenocarcinoma: T1-3N0-1M0, mean age 64±3.2 years. Intact endometrial tissues were obtained during surgical treatment of patients with uterine fibroids (n = 20). All patients gave their written informed consent for the study. Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), estrogen receptors ERα and ERβ, progesterone receptor RP4 and androgen receptors RA were measured by ELISA in samples of tumor and peritumoral (PT) tissues. Statistical processing of results was performed using the Statistica 10. Results: Tumor tissues of patients with EC, regardless of the histological structure, showed higher levels of estrogens and androgens and their receptors, compared with the intact endometrium, without significant changes in levels of progesterone and its receptor. In the main group, compared with the control group, E1 levels in tumors were lower by 1.6 times, E2 by 1.3 times (p &lt; 0.05), but T higher by 2.4 times, ERα by 1.7 times, ERβ by 1.5 times (p &lt; 0.05). PT, compared with the intact endometrium, had lower levels of E1 and E2 by 2 times and 1.5 times, P4 by 5.1 times, and T was lower only in PT with squamous metaplasia by 2.8 times. Levels of all steroid hormone receptors in PT were higher, regardless of the histological type of tumors. In PT of the main group, levels of E1 were 1.3 times lower (p &lt; 0.05) than in controls, P4 – by 2.2 times, T – by 2.8 times, RP4 – by 1.7 times and ERβ by 1.8 times (p &lt; 0.05), but ERα was 3.2 times higher. Conclusions: Tumors with squamous metaplasia, compared with endometrioid adenocarcinoma, are characterized by an imbalance of steroid hormones towards the predominance of androgens, and ERα plays a dominant role among estrogen receptors. The tumor probably synthesizes sex steroids independently and also pumps them over from the surrounding area. At the same time, malignant endometrial tumors, regardless of their histological structure, are more saturated with estrogens, androgens and their receptors, compared with the intact endometrium.
Development and validation of a novel nomogram predicting long-term progression in patients treated with early salvage radiation therapy after radical prostatectomy: The key role of PSA kinetics
Authors: N. Fossati, E. Mazzone, R.J. Karnes, S.A. Boorjian, G. Motterle, A. Bossi, T. Kumar, N. Di Muzio, C. Cozzarini, B. Noris Chiorda, D. Robesti, A. Stabile, G. Gandaglia, N. Suardi, D. Bartkowiak, S.F. Shariat, G. Goldner, S. Joniau, H. Van Poppel, C. Berghen, G. De Meerleer, P. Karakiewicz, F. Montorsi, T. Wiegel, A. Briganti
Journal: European Urology (2022)
Genomic and clinical characteristics of <i><i>MET</i></i> alterations in solid tumors among the 10,475 Chinese patients.
Authors: Yaping Li, Mingwei Li, Yanrui Zhang, Xueyu Hao, Yun Zhang, Xiayuan Liang, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2022)

3115 Background: Somatic alterations of the MET oncogene are emerging as an attractive target in human cancers, thus, understanding the molecular epidemiology of MET alterations is essential. While the occurrence of MET exon 14 skipping mutations (MET ex14) in US lung cancer patients is well defined, it is not widely published for Chinese patients. In addition, reports on the occurrence of METex14 outside lung cancer and other clinically relevant MET alterations across all cancers are limited. Methods: The MET ex14 alterations and amplification data of 10475 Chinese cancer patients from 16 types of cancer were obtained in Acronmed database, including non-small cell lung cancer (NSCLC, n = 5719), Hepatocellular carcinoma (HCC, n = 511), colorectal cancer (CRC, n = 1779), renal cell carcinoma (RCC, n = 1169), Gastric carcinoma (GC, n = 679), etc. Genomic profiling of DNA was performed through a next-generation sequencing. Results: Of all pan-cancer patients, 141 cases (1.3%) with MET alterations were identified, including MET Amp (0.9%) and MET ex14 (0.7%). Compared to Western population (̃3%), the frequency of MET alterations is much lower in Chinese cancer patients (1.3%). MET Amp were most commonly found in HCC (1.7%), GC (1.3%), NSCLC (0.7%), RCC (0.7%), CRC (0.2%). MET ex14 occurred most in NSCLC (0.5%), HCC (0.3%), CRC (0.2%). HCC were significantly to have MET Amp than NSCLC (P = 0.01), while MET ex14 mutations were more likely to be observed in NSCLC (p = 0.02). We further analyzed the MET mutation characteristics of NSCLC. The most frequently co-mutated genes in MET ex14 cohort were TP53 (48%,15/31), KMT2B (23%,7/31) and EGFR (16%, 5/31). Except for TP53 (65%,22/34) and EGFR (56%,19/34) mutations. Interestingly,other gene mutations were rare in the patients with MET Amp. In addition, MET ex14 patients showed significant lower EGFR mutation comparing to the MET amp patients (P = 0.002). Conclusions: Our study demonstrated a landscape of MET alterations among the Chinese population. MET mutations occurs in a variety of solid tumors, indicating that these patients may benefit from MET inhibitors.
The perception and emotional reaction to genetic test results in cancer patients in an immigrant enriched hospital.
Authors: Pooja Gogia Bhasin, Theresa Durana, Nay Yee Wint Kyaw, Vijaya Natarajan, Jacob Best, Angela Wu, Sudhamshi Toom, Yiqing Xu
Journal: Journal of Clinical Oncology (2022)

e24128 Background: Genetic testing detects hereditary cancer syndromes and guides prophylactic surgery, intensive surveillance and family member testing. Despite its surge in use, research studies exploring the cancer patient’s perception and emotional reactions of their genetic test result is sparing. We hypothesized that the patient’s perception may be influenced by their ethnicity, educational level and English speaking status. Methods: Cancer patients who had genetic testing performed in the last 10 years were consented to take a questionnaire survey. The correctness of understanding their genetic test results were studied and compared among various ethnic groups, education levels and first spoken languages. We also evaluated the patient’s emotional reaction towards the result. Results: The data for the first 100 patients were analyzed. The primary tumor sites were breast (n = 71), gynecological (n = 16), gastrointestinal (n = 7), genitourinary (n = 5) and lung (n = 1). Eighteen patients were mutation carriers. The correctness in understanding mutation status was 65.7%, 54.2%, 70% and 45.5% in African American, Asian, Caucasian and Hispanics respectively. The correctness was 60%, 64.5% and 66.67% in patients with education levels of grade school or below, high school, or college or higher respectively. None of the 3 patients who carried a mutation with education level of grade school or lower understood the implications of their mutations. Details of correctness in understanding in patients with and without mutation are provided in the table. The correctness was 61.72% and 63.15% in English speaking vs non-English speaking patients. Patients could recall pre-test counseling in 76% and posttest counseling in 67% of cases. Among mutation carriers, 22.2% had anxiety or stressful feelings about the test result, while in patients with no mutation, 20.7% had anxiety/depression. 67% patients carried out prophylactic surgery as recommended. Conclusions: The correctness of understanding their genetic test results across all ethnic groups, education levels and language was below 70%. Patients with education level below grade school encountered in the immigrant population need more attention. Improvement in communication and patient education is imperative in order to carry out recommendations. Structured emotional support to the patient should always complement genetic counseling and testing.[Table: see text]